The studies proposed for this Allergy Diseases Center include four projects. All of these directly relate to the pathophysiology, diagnosis, and treatment of respiratory allergies. We are interested in the factors responsible for the exquisite bronchial sensitivity of patients with bronchial asthma to histamine, acetylcholine, and their specific allergens. A major approach will be to determine the natural course of the bronchial sensitivity in patients with bronchial asthma and/or allergic rhinitis. We will attempt to delineate those factors that pertain to the pathophysiologic mechanism of bronchial sensitivity in relation to beta adrenergic blockage as well as this relationship to cholinergic stimulation. We will study respiratory tract secretions and mediators contained in these secretions following inhalation challenge with specific allergens. We will also attempt to correlate the physical properties with the immunochemical aspects of bronchial mucus. The relation between the immunologic and pharmacologic aspects of hypersensitivity will be investigated by studying the effect of pertussis vaccine and chronic administration of beta adrenergic blocking agents on reaginic antibody production. Preliminary investigations of all projects has been completed either in relation to basic research which is applicable to the development of appropriate methodology. Although the various projects are interrelated by their relation to mechanisms of hypersensitivity to pharmacological mediators on the respiratory tract, they are listed and described as separate projects. 1. The Natural History of Asthma; 2. Comparison of Bronchial Sensitivity to Mediators as an Index of Adrenergic Abnormality; 3. Relationship of the Immunologic and Pharmacologic Aspects of Asthma; 4. Sputum Studies.